Atherosclerosis is a major cause of morbidity and mortality in the United States and Western European countries. Hypercholesterolemia, especially increased levels of low density lipoprotein (LDL) cholesterol, has been shown to be related to an increased risk of coronary heart disease (CHD) (Lowering blood cholesterol to prevent heart disease: NIH consensus development conference statement. (1985) Arteriosclerosis 5: 404-412). In the United States alone, hypercholesterolemia contributes to 1.5 million myocardial infarctions per year and up to 0.5 million people die as a direct result of atherosclerotic cardiovascular disease (Lipid Research Clinics Program. The Lipid Research Clinics primary prevention trial results: the relationship of reduction in incidence of coronary heart disease to cholesterol lowering. (1984) JAMA 251: 365-374). It is estimated that as many as 40 million people in the United States between the ages of 40 to 70 years have high cholesterol levels and are candidates for lipid-lowering therapy. The National Cholesterol Education Program (NCEP), sponsored by the National Heart, Lung and Blood Institute, is a major national effort to educate physicians and the public about the risks associated with high blood cholesterol levels. In addition, the NCEP has suggested guidelines to identify and treat patients with high serum cholesterol (Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. (1988) Arch. Intern. Med. 148: 36-69).
There is substantial evidence that lowering total and LDL cholesterol reduce the risk of CHD. Of particular interest are the outcomes of several angiographic trials of decreased total and LDL cholesterol (Blankenhorn, D. H., Nessim, S. A., Johnson, R. L. et al. (1987) Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA 257: 3233-3240. Brensike, J. F., Levy, R. I., Kelsey, S. F. et al. (1984) Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study. Circulation 69: 313-324. Brown, G., Albers, J. J., Fisher, L. D. et al. (1990) Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N. Engl. J. Med. 323: 1289-1298. Buchwald, H., Varco, R. L., Matts, J. P. et al. (1990) Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia: report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N. Engl. J. Med. 323: 946-955. Cashin-Hemphill, L., Mack, W. J., Pogoda, J. et al. (1990) Beneficial effects of colestipol-niacin on coronary atherosclerosis: a 4-year follow-up. JAMA 264: 3013-3017. Kane, J. P., Malloy, M. J., Ports, T. A. et al. (1990) Regression of coronary atherosclerosis during treatment of familial hypercholesterolemia with combined drug regimens. JAMA 264: 3007-3012. Ornish, D., Brown, S. E., Sherwitz, L. W. et al. (1990) Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet 336: 129-133.). These studies in patients with high, average or low baseline cholesterol levels achieved cholesterol reductions with drugs, partial ileal bypass or diet. These studies provided evidence that cholesterol reduction can slow the progression of atherosclerotic lesions, and actually induce regression of existing lesions. Therefore, there is convincing evidence that lowering total and LDL cholesterol is beneficial (Rifkind, B. M. and Grouse, L. D. (1990) Cholesterol redux. JAMA 264: 3060-3061. LaRosa, J. C. and Cleeman, J. I. (1992) Cholesterol lowering as a treatment for established coronary heart disease. Circulation 85: 1229-1235) not only in terms of primary prevention of CHD but also in secondary prevention.